RESUMO
Mesenchymal stem cells (MSCs) are adult stem cells from mesoderm with multi potential differentiation, and are being widely studied as a promising treatment for autoimmune diseases. The main inflammatory factors of experimental autoimmune uveitis (EAU) are T helper type 1 (Th1) and Th17. Regulatory B cells (Bregs) are a newly designated B cell subgroup, which has been proved to play a key role in regulating inflammation, autoimmunity and cancer. In this regard, we establish the EAU model by injecting interphotoreceptor retinoid-binding protein combined with complete Freund's adjuvant into the tail vein and bilateral thighs of rats, and inject MSCs or equal volume of phosphate buffer saline intraperitoneally on the day of immunization. Dynamic changes of cell subsets and cytokine expression are tested at different time periods to explore the relationship between MSCs treatment and disease prognosis during EAU course. Our results suggest that compared with the model control group, MSCs treatment can significantly reduce the production of Th1 and Th17 cytokines during EAU, while the production of regulatory B cells (Bregs) cytokines is significantly increased. At the same time, MSCs can reduce the proportion of Th17 in lymphocytes while the proportion of Bregs is elevated, thus inhibiting the differentiation and activity of interleukin in EAU rats. All this results provide more powerful evidence for cell therapy of autoimmune uveitis.
Assuntos
Linfócitos B Reguladores , Células-Tronco Mesenquimais , Uveíte , Animais , Linfócitos B Reguladores/metabolismo , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Células Th1 , Uveíte/metabolismo , Uveíte/terapiaRESUMO
The chapter is a review enclosed in the volume "Glaucoma: A pancitopatia of the retina and beyond." No cure exists for glaucoma. Knowledge on the molecular and cellular alterations underlying glaucoma neurodegeneration (GL-ND) includes innovative and path-breaking research on neuroinflammation and neuroprotection. A series of events involving immune response (IR), oxidative stress and gene expression are occurring during the glaucoma course. Uveitic glaucoma (UG) is a prevalent acute/chronic complication, in the setting of chronic anterior chamber inflammation. Managing the disease requires a team approach to guarantee better results for eyes and vision. Advances in biomedicine/biotechnology are driving a tremendous revolution in ophthalmology and ophthalmic research. New diagnostic and imaging modalities, constantly refined, enable outstanding criteria for delimiting glaucomatous neurodegeneration. Moreover, biotherapies that may modulate or inhibit the IR must be considered among the first-line for glaucoma neuroprotection. This review offers the readers useful and practical information on the latest updates in this regard.
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Inteligência Artificial , Terapia Biológica , Glaucoma , Inflamação , Degeneração Neural , Uveíte , Glaucoma/diagnóstico por imagem , Glaucoma/imunologia , Glaucoma/metabolismo , Glaucoma/terapia , Humanos , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/terapia , Degeneração Neural/diagnóstico por imagem , Degeneração Neural/imunologia , Degeneração Neural/metabolismo , Degeneração Neural/terapia , Uveíte/diagnóstico por imagem , Uveíte/imunologia , Uveíte/metabolismo , Uveíte/terapiaRESUMO
BACKGROUND: Uveitis is an inflammatory and heterogeneous ocular disorder and has a profound impact on patients' life, work and family. There are substantial costs to the countries and individuals associated with treatment of the complications of uveitis and blindness. Conventional therapies did not lead to satisfactory outcomes for uveitis and are associated with substantial adverse events (AEs). Emerging evidences have proved the important value and potential prospect of Chinese medicines and its compound in uveitis. However, although Chinese medicines are widely used in uveitis, its therapeutic effect and safety are still controversial. It is, therefore, timely to perform an objective and normative systematic review to assess the efficacy and safety of Chinese medicines in treating uveitis on current research. METHODS: The systematic review will include all of the randomized controlled trials (RCT) on the efficacy and safety of Chinese medicines for uveitis. A relevant literature search by sensitive search strategies was conducted using the following electronic databases from their inception to September 30, 2019: PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal database (VIP) and Chinese Biomedical Literature database (CBM). The strategy combines treatment terms and disease: that is, "Medicine, Chinese Traditional" (e.g., "Medicine, Chinese Traditional", TCM, Traditional Chinese medicine, Zhong Yi Xue) and uveitis. We will also search registers of clinical trials, potential gray literature, and conference abstracts. There are no limits on language and publication status. The literature screening, data extraction, and quality assessment will be conducted by 2 reviewers independently. The reporting quality and risk of bias will be assessed by other two researchers. Best-corrected visual acuity (BCVA) and improvement in disease activity were assessed as the primary outcome. The secondary outcomes will include laboratory efficacy indexes, score changes in the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25), uveitis-related tissue damage or complications, concurrent requirement of corticosteroids, immunosuppressive drugs or biologics, and AEs of treatment. Meta-analysis will be performed using RevMan5.3 software provided by the Cochrane Collaboration. RESULTS: This study will provide a comprehensive review based on current evidence of Chinese medicines treatment for uveitis in several aspects, including BCVA and improvement in disease activity, laboratory efficacy indexes, score changes in the NEI-VFQ 25, uveitis-related tissue damage or complications, etc. CONCLUSION:: The conclusion of this study will provide evidence to determine whether Chinese medicines are an effective and safe intervention for patients with uveitis. ETHICS AND DISSEMINATION: It is not necessary to obtain ethical approval for this study, given that this protocol is for a systematic review. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020153620.
Assuntos
Medicina Tradicional Chinesa/métodos , Uveíte/terapia , Humanos , Metanálise como Assunto , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Biologics are increasingly used in management of Behçet's Disease (BD) including ocular BD, but the evidence base is limited, mostly from studies of uveitis and BD manifestations. OBJECTIVE: To review the evidence base for biologics in the treatment of ocular BD. METHODS: Systematic literature search was made using exploded key words-Behçet's, ocular, biologics in MEDLINE, Cochrane library, Database of Abstracts Reviews and Effects, Clinical Trials.gov, Science Direct and Google Scholar. There was no limitation on region, language or date (Search updated 16th October 2018). Literature retrieval was restricted to randomised controlled trials (RCTs) of biologics. RESULTS: Of 237 papers retrieved, eight met the inclusion criteria. RCTs on interferon alpha 2a (INF-α 2a), adalimumab, secukinumab, gevokizumab, rituximab and daclizumab were retrieved (two for adalimumab and gevokizumab). The outcome measures were not met for secukinumab, daclizumab and gevokizumab. Rituximab and INF-α 2a showed promising preliminary results but sufficiently powered RCTs are needed to provide adequate evidence of efficacy. The RCTs on adalimumab did not evaluate efficacy for BD uveitis specifically, hence are of limited value for this review. CONCLUSION: Some biologics show promise in treating BD uveitis, but more RCTs are needed for firm conclusions about efficacy. A phase IV study or, registry of adalimumab could provide data on its efficacy in BD uveitis compared to other forms.
Assuntos
Síndrome de Behçet/terapia , Fatores Biológicos/uso terapêutico , Terapia Biológica/métodos , Uveíte/terapia , Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Daclizumabe/uso terapêutico , Humanos , Interferon-alfa/uso terapêutico , Rituximab/uso terapêuticoRESUMO
Los agentes biológicos han irrumpido como una alternativa eficaz en el tratamiento de las uveítis no-infecciosas, especialmente en cuadros refractarios a inmunosupresores convencionales, con buena tolerancia y rápido efecto. Hay patologías como la enfermedad de Behçet en que incluso pueden estar indicados como tratamiento de primera línea. Este artículo ayudará a reconocer las patologías específicas donde presentan mayor eficacia, entrega herramientas para escoger el agente más adecuado para cada paciente y sugiere estrategias para evitar la pérdida de control de la enfermedad en el largo plazo.
Biological therapies have emerged as an effective option for the treatment of non-infectious uveitis, especially in refractive cases to conventional immunosup-pressive drugs. They are fast-acting, well tolerated, and can be considered as first-line agents for the treatment of certain uveitis like in Behçet Ìs disease. This article will aid in identifying the uveitis syndromes where biological therapy is more effective, help choosing the most appropriate agent for a particular case and offer suggestions on how to keep long-term disease control.
Assuntos
Humanos , Uveíte/terapia , Fatores Biológicos/uso terapêutico , Terapia Biológica , Chile , Síndrome de Behçet/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Imunossupressores/uso terapêuticoRESUMO
PURPOSE OF REVIEW: The aim of this review is to highlight recent changes in the treatment of juvenile idiopathic arthritis (JIA) - associated uveitis in the era of biologics. RECENT FINDINGS: Early introduction of steroid-sparing therapies is paramount for appropriate management. Biologic therapies have improved the therapeutic management of JIA-uveitis and adalimumab is currently approved for pediatric-onset noninfectious chronic anterior uveitis with an inadequate response to topical steroids and methotrexate. Recent studies suggest that ocular complications in JIA-uveitis are less frequent compared with previous publications. However, patients with JIA-uveitis seem to be particularly dependent on classical immunosuppressive drugs or biologics. Indications for primary lens implantation have expanded considerably with the evolution of materials and better control of inflammation with biologics. The rate of serious adverse events related to new therapeutic approaches seem acceptable, however longer term follow-up is necessary. SUMMARY: Improvement in the initial screening and improved inflammation control with biologics has considerably reduced the potentially sight-threatening prognosis of JIA-uveitis.
Assuntos
Artrite Juvenil/terapia , Terapia Biológica , Uveíte/terapia , Adalimumab/uso terapêutico , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Criança , Humanos , Metotrexato/uso terapêutico , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
The uveitides are a heterogenous group of ocular inflammatory disorders that account for the third highest cause of blindness worldwide, responsible for 5-10% of visual impairment globally. Up to 35% of patients with uveitis can suffer significant vision loss. To prevent irreversible structural damage and blindness, it is important that the diagnosis and commencement of appropriate therapy occurs promptly. Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin. Significant progress has been made in the past decade in our understanding of the immunopathological pathways that drive intraocular inflammation, allowing the development of targeted therapy with biologic agents. These include TNF-α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept. The efficacy of these agents has been studied in cases of severe uveitis that are refractory to conventional immunomodulatory agents and provide exciting results that have revolutionised uveitis management. Though the biologic era has provided a large armamentarium to treat uveitis, ongoing challenges and cases of recalcitrant uveitis remain, posing a challenge to internal medicine physicians. This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 and 2018 using PubMed, EMBASE, Ovid MEDLINE and Cochrane libraries.
Assuntos
Fatores Biológicos/uso terapêutico , Terapia Biológica/tendências , Uveíte/terapia , Corticosteroides/uso terapêutico , Citocinas/antagonistas & inibidores , Gerenciamento Clínico , Humanos , Imunossupressores/uso terapêutico , Terapia de Alvo Molecular , Uveíte/imunologiaRESUMO
The interleukin (IL)-23/IL-17 axis plays a central role in the pathogenesis of immune-mediated diseases such as psoriasis, psoriatic arthritis, Crohn's disease, and uveitis. Therefore, targeting the IL-23/IL-17 axis has become the focus of multiple clinical trials for drug development in patients with autoimmune diseases. We briefly describe the biology of the IL-23/IL-17 axis and its relevance to the pathogenesis of experimental and clinical uveitis, and review the monoclonal antibody therapies targeting this pathway. Finally, 2 ongoing phase 2 trials of the anti-IL-23 biologic therapy ustekinumab (STELARA, Janssen Biotech Inc, Horsham, PA) in patients with noninfectious uveitis are introduced.
Assuntos
Doenças Autoimunes/terapia , Terapia Biológica , Interleucina-23/imunologia , Uveíte/terapia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Ensaios Clínicos como Assunto , Fármacos Dermatológicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Interleucina-17/imunologia , Células Th17/imunologia , Pesquisa Translacional Biomédica , Ustekinumab/uso terapêutico , Uveíte/imunologiaRESUMO
BACKGROUND: There is a paucity of data on the ocular outcomes in paediatric non-infectious uveitis since the introduction of the biologic agents. The purpose of this study was to outline the clinical characteristics of children with non-infectious uveitis and determine the visual outcomes and ocular complication rates in the modern era. METHODS: Children with non-infectious uveitis from January 2011 to December 2015 were identified. Data was collected at baseline, 1, 3, 5, and 10 years post diagnosis. The incidence rates of visual impairment, structural ocular complications and surgical intervention were calculated. Using logistic regression the association between various baseline characteristics and later visual impairment was investigated. RESULTS: Of the 166 children, 60.2% (n = 100) had a systemic disease association. 72.9% (n = 121) children received methotrexate, 58 children progressed to a biologic. The incidence rates of visual acuity loss to > 0.3 LogMAR (6/12) and to ≥1.0 LogMAR (6/60) were 0.05/Eye Year (EY) and 0.01/EY, respectively. Visual outcomes in the Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) and Idiopathic Uveitis cohorts were not statistically significant. Of the 293 affected eyes, posterior synechiae was the predominant complication on presentation, while cataract had the highest incidence rate (0.05/EY). On direct comparison, children with JIA-U were statistically significantly more likely to develop glaucoma while children with Idiopathic Uveitis were statistically significantly more likely to develop macular oedema. CONCLUSION: One third of children received a biological therapy, reflecting increasing utilisation and importance of biological agents in the management of inflammatory conditions. Rates of visual impairment and ocular complications are an improvement on previously published data.
Assuntos
Terapia Biológica/métodos , Uveíte/terapia , Transtornos da Visão/epidemiologia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Uveíte/complicações , Transtornos da Visão/etiologiaRESUMO
In this study, we evaluated the preventive and curative effects of ethanolic extract of Propolis (EEP) during α-Tropomyosin-induced uveitis in an experimental model using Wistar rats, through the regulation of inducible nitric oxide synthase (NOS2) and arginase-1. In this context, rats received daily injection of EEP (100 mg/kg) for 5 days prior to immunization or for 9 days commencing 5 days post immunization with α-Tropomyosin extract, then were sacrificed at day 14. Histological examination, NOS2, arginase-1, and nuclear factor-κB (NF-κB) expression were evaluated in the retinas. Plasmatic production of nitric oxide (NO), urea, IL-4, and TNF-α was assessed. We have found that treatment with EEP substantially reduced the retinal histological damages induced by α-Tropomyosin. In the same context, a significant decrease of NO and TNF-α levels was noticed. Interestingly, EEP down-modulated NOS2 and NF-κB expression in retina. Also, an increase in urea and IL-4 levels was concomitant to an up-modulation of arginase-1 expression. Hence, it appears that EEP attenuated retinal damages through the induction of Th2 response and the inhibition of NF-κB/NOS2 pathway.
Assuntos
Apiterapia/métodos , Doenças Autoimunes/terapia , Própole/farmacologia , Uveíte/terapia , Animais , Arginase/metabolismo , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Etanol/química , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Própole/administração & dosagem , Ratos , Ratos Wistar , Células Th2/imunologia , Tropomiosina/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Uveíte/imunologiaRESUMO
Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).
Assuntos
Guias de Prática Clínica como Assunto , Uveíte/terapia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , Prova Pericial , Humanos , Imunossupressores/uso terapêutico , Guias de Prática Clínica como Assunto/normas , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse.
Assuntos
Terapia Biológica , Antígeno HLA-B27/imunologia , Espondiloartropatias/terapia , Uveíte/terapia , Glucocorticoides/uso terapêutico , Humanos , Midriáticos/uso terapêutico , Espondiloartropatias/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/imunologiaRESUMO
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.
Assuntos
Artrite Juvenil , Terapia Biológica/métodos , Imunossupressores/farmacologia , Uveíte , Artrite Juvenil/complicações , Artrite Juvenil/imunologia , Doenças Assintomáticas , Autoimunidade/efeitos dos fármacos , Criança , Diagnóstico Precoce , Interação Gene-Ambiente , Humanos , Programas de Rastreamento/métodos , Prognóstico , Uveíte/diagnóstico , Uveíte/etiologia , Uveíte/fisiopatologia , Uveíte/terapiaRESUMO
Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials conducted in the last 12 years for the treatment of AU are summarized and critically discussed.
Assuntos
Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/terapia , Uveíte/fisiopatologia , Uveíte/terapia , Corticosteroides/uso terapêutico , Autoantígenos/imunologia , Linfócitos B/imunologia , Terapia Biológica/métodos , Humanos , Imunossupressores/uso terapêutico , Linfócitos T/imunologiaRESUMO
Biologic agents are a group of therapeutic agents targeting mediators of inflammation, including soluble factors (e.g. cytokines and chemokines), cytokine/chemokine receptors and immune cell surface markers. The purpose of this chapter is to introduce the use of biologic therapies for the treatment of ocular inflammatory diseases. Anti-tumor necrosis factor agents, particularly infliximab and adalimumab, are well studied. We will review these, as well as newer options in the development of more targeted therapy, including anti-interleukins, anti-cell surface molecule biologics and interferon-2α. Biologic treatment of ocular inflammatory disease has advanced rapidly over the past 10 years and continues to be an exciting field of study.
Assuntos
Terapia Biológica/métodos , Fatores Imunológicos/uso terapêutico , Interleucinas/antagonistas & inibidores , Rituximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/terapia , Terapia Biológica/efeitos adversos , Humanos , Fatores Imunológicos/efeitos adversos , Rituximab/efeitos adversosRESUMO
Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective therapies for each entity have not been defined.
Assuntos
Anti-Inflamatórios/uso terapêutico , Terapia Biológica , Uveíte/terapia , Animais , Apresentação de Antígeno/efeitos dos fármacos , Terapia Biológica/tendências , Citocinas/antagonistas & inibidores , Humanos , Ativação Linfocitária/efeitos dos fármacos , Terapia de Alvo Molecular , Uveíte/imunologiaRESUMO
Objetivos: evaluar el tratamiento farmacológico e identificar los factores pronósticos en una evolución clínica desfavorable con uveítis crónicas y recurrentes no infecciosas, en el Instituto Cubano Oftalmología Ramón Pando Ferrer durante el período 2012-2013. Métodos: se realizó un estudio de utilización de medicamentos. Se efectuó un diseño de cohorte retrospectivo evaluativo y un estudio transversal analítico de factores pronósticos. Fueron evaluados 116 pacientes. Las variables utilizadas correspondieron a la evaluación farmacoterapéutica: selección del medicamento, pauta de administración y causas de incumplimiento terapéutico. Para la evolución clínica desfavorable se analizaron variables sociodemográficas y clínicas. Se calcularon frecuencias absolutas y relativas. Se realizó un análisis univariado. Las variables significativas a la evolución se incluyeron en el modelo de regresión logística múltiple. Resultados: no existieron errores en la prescripción en el 100 por ciento de los evaluados. El 15,5 por ciento de los pacientes no cumplieron con el tratamiento prescrito; 83,3 por ciento se relacionó con la presencia de reacciones adversas y 33,3 por ciento con la falta de disponibilidad. El 57 por ciento presentó efectos adversos por corticoesteroides y el 39 por ciento por inmunosupresores. El curso clínico crónico y la localización resultaron factores influyentes en una evolución desfavorable. Conclusiones: la evaluación farmacoterapéutica en el caso de las uveítis crónicas es adecuada. No existen errores en la prescripción. Las causas más frecuentes de incumplimiento terapéutico son la suspensión del tratamiento por efectos adversos, la falta de disponibilidad de inmunosupresores y la alternativa biológica. El curso clínico crónico y la localización de las uveítis pueden considerarse como un factor pronóstico en la evolución desfavorable de esta enfermedad(AU)
Objectives: to evaluate the pharmacological treatment and to identify the predictive factors in unfavorable clinical progression of patients with non-infectious recurrent and chronic uveitis at Ramon Pando Ferrer Cuban Institute of Ophthalmology in the period of 2012 to 2013. Methods: drug use study was conducted based on a design of retrospective evaluative cohort and a cross-sectional analytical study of predictive factors. One hundred and sixteen patients were evaluated. The variables corresponded to the pharmacological treatment evaluation: selection of drug, administration guidelines and causes of non-adherence to treatment. For the unfavorable clinical progression, the sociodemographic and clinical variables were considered. Absolute and relative frequencies were calculated; the univariate analysis was made and the significant variables for progression were included in the multiple logistic regression model. Results: there was no error in prescribing 100 percent of the evaluated cases. In the group, 15,5 percent of patients did not adhere to the prescribed treatment; 83,3 percent due to adverse reactions and 33,3 percent to lack of drug availability. Fifty seven percent suffered adverse effects from corticosteroids and 39 percent from immunosupressors. The chronic clinical course and the location were the most influential factors in the unfavorable progression. Conclusions: the pharmacological treatment evaluation for the chronic uveitis is adequate. There are no errors in prescription. The most frequent causes of non-adherence to treatment are cessation of treatment on account of adverse effects, lack of availability of immunosupressors and biological alternative. The chronic clinical course and the location of uveitis can be considered as predictive factors in the unfavorable progression of the disease.(AU)
Assuntos
Humanos , Uveíte/terapia , Avaliação de Medicamentos/métodos , Evolução Clínica/estatística & dados numéricos , Estudos Transversais , Estudos Retrospectivos , Estudos de CoortesRESUMO
OBJETIVOS: evaluar el tratamiento farmacológico e identificar los factores pronósticos en una evolución clínica desfavorable con uveítis crónicas y recurrentes no infecciosas, en el Instituto Cubano Oftalmología "Ramón Pando Ferrer" durante el período 2012-2013. MÉTODOS: se realizó un estudio de utilización de medicamentos. Se efectuó un diseño de cohorte retrospectivo evaluativo y un estudio transversal analítico de factores pronósticos. Fueron evaluados 116 pacientes. Las variables utilizadas correspondieron a la evaluación farmacoterapéutica: selección del medicamento, pauta de administración y causas de incumplimiento terapéutico. Para la evolución clínica desfavorable se analizaron variables sociodemográficas y clínicas. Se calcularon frecuencias absolutas y relativas. Se realizó un análisis univariado. Las variables significativas a la evolución se incluyeron en el modelo de regresión logística múltiple. RESULTADOS: no existieron errores en la prescripción en el 100 % de los evaluados. El 15,5 % de los pacientes no cumplieron con el tratamiento prescrito; 83,3 % se relacionó con la presencia de reacciones adversas y 33,3 % con la falta de disponibilidad. El 57 % presentó efectos adversos por corticoesteroides y el 39 % por inmunosupresores. El curso clínico crónico y la localización resultaron factores influyentes en una evolución desfavorable. CONCLUSIONES: la evaluación farmacoterapéutica en el caso de las uveítis crónicas es adecuada. No existen errores en la prescripción. Las causas más frecuentes de incumplimiento terapéutico son la suspensión del tratamiento por efectos adversos, la falta de disponibilidad de inmunosupresores y la alternativa biológica. El curso clínico crónico y la localización de las uveítis pueden considerarse como un factor pronóstico en la evolución desfavorable de esta enfermedad.
OBJECTIVES: to evaluate the pharmacological treatment and to identify the predictive factors in unfavorable clinical progression of patients with non-infectious recurrent and chronic uveitis at "Ramon Pando Ferrer" Cuban Institute of Ophthalmology in the period of 2012 to 2013. METHODS: drug use study was conducted based on a design of retrospective evaluative cohort and a cross-sectional analytical study of predictive factors. One hundred and sixteen patients were evaluated. The variables corresponded to the pharmacological treatment evaluation: selection of drug, administration guidelines and causes of non-adherence to treatment. For the unfavorable clinical progression, the sociodemographic and clinical variables were considered. Absolute and relative frequencies were calculated; the univariate analysis was made and the significant variables for progression were included in the multiple logistic regression model. RESULTS: there was no error in prescribing 100 % of the evaluated cases. In the group, 15,5 % of patients did not adhere to the prescribed treatment; 83,3 % due to adverse reactions and 33,3 % to lack of drug availability. Fifty seven percent suffered adverse effects from corticosteroids and 39% from immunosupressors. The chronic clinical course and the location were the most influential factors in the unfavorable progression. CONCLUSIONS: the pharmacological treatment evaluation for the chronic uveitis is adequate. There are no errors in prescription. The most frequent causes of non-adherence to treatment are cessation of treatment on account of adverse effects, lack of availability of immunosupressors and biological alternative. The chronic clinical course and the location of uveitis can be considered as predictive factors in the unfavorable progression of the disease.
Assuntos
Humanos , Uveíte/terapia , Evolução Clínica/estatística & dados numéricos , Avaliação de Medicamentos/métodos , Estudos Transversais , Estudos Retrospectivos , Estudos de CoortesRESUMO
PURPOSE OF REVIEW: Pediatric uveitis is relatively uncommon, accounting for only 5-10% of all patients with uveitis. However, owing to high prevalence of complications and devastating outcomes, its lifetime burden can be significant. RECENT FINDINGS: Immunomodulatory therapy has been associated with better outcomes in noninfectious pediatric uveitis. However, effective treatments are limited by medication-related complications, including multiorgan toxicities and systemic side effects. SUMMARY: We review the current therapies available to treat pediatric uveitis, discuss novel and future therapies, and provide clinical recommendations utilizing these new agents. The consideration for treatment regimens in noninfectious pediatric uveitis is multifactorial. Understanding past, present, and future technology will aid in treatment of a complex and refractory disease.